U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C19H21FN4
Molecular Weight 324.396
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TECASTEMIZOLE

SMILES

c1ccc2c(c1)[nH]c(=NC3CCNCC3)n2Cc4ccc(cc4)F

InChI

InChIKey=SFOVDSLXFUGAIV-UHFFFAOYSA-N
InChI=1S/C19H21FN4/c20-15-7-5-14(6-8-15)13-24-18-4-2-1-3-17(18)23-19(24)22-16-9-11-21-12-10-16/h1-8,16,21H,9-13H2,(H,22,23)

HIDE SMILES / InChI

Molecular Formula C19H21FN4
Molecular Weight 324.396
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Tecastemizole (aka Norastemizole) is an H1 receptor antagonist that showed great promise as potential next-generation antihistamine allergy medication. Sepracor developed Norastemizole through phase III clinical trials; however, the FDA rejected the application for approval on the grounds of an unacceptable profile of adverse side-effects including phospholipidosis and cardiomyopathies in animals exposed to the drug.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: Q12809|||Q9BUT7
Gene ID: 3757.0
Gene Symbol: KCNH2
Target Organism: Homo sapiens (Human)
27.7 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Effect of tecastemizole on pulmonary and cutaneous allergic inflammatory responses.
2007 Jun
Patents

Sample Use Guides

In a phase III clinical trial, a single oral dose of norastemizole (25 mg oral) was shown to significantly attenuate the histamine-induced wheal and flare response within 30 minutes.
Route of Administration: Oral
HEK-293 cells stably transfected with the human ether-a go-go-related gene (HERG) K+ channel were cultured in minimal essential medium supplemented with 10% fetal bovine serum and 400 micro-g/mL G418. Norastemizole was dissolved in absolute ethanol and diluted to experimental concentrations with extracellular HEPES-buffered in Tyrode's solution. Cell voltage was recorded under steady-state drug block conditions at several concentrations of norastemizole. Norastemizole was observed to block the HERG current, but required higher concentrations and produced an incomplete block relative to comparator compounds. Norastemizole was estimated to have an IC50 of 27.7 nM and a maximum HERG current block of 48%.
Substance Class Chemical
Created
by admin
on Sat Jun 26 03:30:40 UTC 2021
Edited
by admin
on Sat Jun 26 03:30:40 UTC 2021
Record UNII
W5DCO14M05
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TECASTEMIZOLE
INN   USAN  
INN   USAN  
Official Name English
R-43512
Code English
1H-BENZIMIDAZOL-2-AMINE,1-((4-FLUOROPHENYL)METHYL)-N-4-PIPERIDINYL-
Common Name English
1-(4-FLUOROBENZYL)-N-(4-PIPERIDINYL)-1H-BENZIMIDAZOL-2-AMINE
Systematic Name English
TECASTEMIZOLE [INN]
Common Name English
NORASTEMIZOLE
Common Name English
TECASTEMIZOLE [USAN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C29578
Created by admin on Sat Jun 26 03:30:40 UTC 2021 , Edited by admin on Sat Jun 26 03:30:40 UTC 2021
Code System Code Type Description
INN
8169
Created by admin on Sat Jun 26 03:30:40 UTC 2021 , Edited by admin on Sat Jun 26 03:30:40 UTC 2021
PRIMARY
DRUG BANK
DB06457
Created by admin on Sat Jun 26 03:30:40 UTC 2021 , Edited by admin on Sat Jun 26 03:30:40 UTC 2021
PRIMARY
NCI_THESAURUS
C76065
Created by admin on Sat Jun 26 03:30:40 UTC 2021 , Edited by admin on Sat Jun 26 03:30:40 UTC 2021
PRIMARY
FDA UNII
W5DCO14M05
Created by admin on Sat Jun 26 03:30:40 UTC 2021 , Edited by admin on Sat Jun 26 03:30:40 UTC 2021
PRIMARY
PUBCHEM
123618
Created by admin on Sat Jun 26 03:30:40 UTC 2021 , Edited by admin on Sat Jun 26 03:30:40 UTC 2021
PRIMARY
MESH
C106448
Created by admin on Sat Jun 26 03:30:40 UTC 2021 , Edited by admin on Sat Jun 26 03:30:40 UTC 2021
PRIMARY
EPA CompTox
75970-99-9
Created by admin on Sat Jun 26 03:30:40 UTC 2021 , Edited by admin on Sat Jun 26 03:30:40 UTC 2021
PRIMARY
CAS
75970-99-9
Created by admin on Sat Jun 26 03:30:40 UTC 2021 , Edited by admin on Sat Jun 26 03:30:40 UTC 2021
PRIMARY
ChEMBL
CHEMBL61301
Created by admin on Sat Jun 26 03:30:40 UTC 2021 , Edited by admin on Sat Jun 26 03:30:40 UTC 2021
PRIMARY
Related Record Type Details
OFF-TARGET->INHIBITOR
HERG channels were expre.ssed in a mammalian (HEK 293) cell line and studied using the patch clamp technique. HKRG current
BINDING
IC50
Related Record Type Details
PARENT -> METABOLITE ACTIVE
Related Record Type Details
ACTIVE MOIETY